{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T14:18:31Z","timestamp":1781187511838,"version":"3.54.1"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Special Project of Performance Incentive Guidance for Scientific Research Institutions in Chongqing","award":["stc2021Mli30020"],"award-info":[{"award-number":["stc2021Mli30020"]}]},{"name":"Chongqing Medical Scientific Research Project","award":["2021ZY014268"],"award-info":[{"award-number":["2021ZY014268"]}]},{"name":"Joint Project of Jiangbei District Health Commission and Science and Technology Bureau","award":["JBKW2022zy002"],"award-info":[{"award-number":["JBKW2022zy002"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"\n Background<\/jats:title>\n Currently, therapeutic approaches for ulcerative colitis (UC), such as aminosalicylates, glucocorticoids, and biologics, exhibit certain efficacy but are hindered by limitations including side effects, high costs, or suboptimal responses. As a traditional Chinese medicine component, berberine (BBR) possesses anti-inflammatory properties and the ability to modulate the gut microbiota, with low toxicity, and may provide new directions for UC treatment in the future.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A mouse UC model was established via dextran sulfate sodium (DSS) induction, and dose-and time-dependent screening was performed to determine the optimal BBR dosage and intervention duration for subsequent experiments. The disease activity index (DAI) and colon length were measured. Colonic tissue changes were observed via HE staining. Serum cytokine levels (IL-1\n \u03b2<\/jats:italic>\n , TNF-\n \u03b1<\/jats:italic>\n , IL-10, TGF-\n \u03b2<\/jats:italic>\n ) were detected using ELISA. The expression levels of ZO-1 and Occludin in mouse colonic tissues were detected by WB. Further analyses included 16S rRNA sequencing to assess gut microbiota diversity and composition, untargeted metabolomics to identify differential metabolites in intestinal tissues, and Mendelian randomization (MR) analysis to explore causal associations among intestinal genes, circulating metabolites, and key bacterial genera. Finally, functional validation was performed by inhibiting the PDGFA receptor.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Berberine significantly alleviated the DAI score, colonic pathological damage, and cytokine imbalance in UC mice, as well as restored mucosal barrier integrity, with the most pronounced effects observed in the UC\u202f+\u202flow-BBR 14\u202fdays group. Gut microbiota analysis revealed distinct microbial structures across groups, with the UC\u202f+\u202flow-BBR 14\u202fdays group showing significantly higher relative abundances of\n Bacteroides<\/jats:italic>\n ,\n Alistipes<\/jats:italic>\n , and\n unclassified_Clostridia_vadinBB60_group<\/jats:italic>\n compared to the UC group (\n p<\/jats:italic>\n \u202f&lt;\u202f0.05). Metabolomics analysis indicated that berberine altered the composition of intestinal tissue metabolites and metabolic pathways. MR analysis demonstrated inverse causal associations between PDGFA and lithocholate sulfate, as well as between lithocholate sulfate and\n Alistipes<\/jats:italic>\n . Additionally, inhibition of the PDGFA receptor reversed the therapeutic effects of BBR, exacerbating inflammatory responses and intestinal mucosal barrier damage. Finally, the correlation analysis between gut microbiota and metabolites also confirmed that the abundance of the genus\n Alistipes<\/jats:italic>\n exhibited a highly significant negative correlation with lithocholate sulfate levels (\n p<\/jats:italic>\n &lt;\u202f0.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Berberine ameliorates symptoms of UC in mice by regulating gut microbiota and metabolite composition. MR analysis first establishes a unidirectional causal chain of PDGFA\/lithocholate sulfate\/\n Alistipes<\/jats:italic>\n , and animal experiments confirm that blocking the PDGFA receptor reverses its therapeutic effects and aggravates inflammation and intestinal mucosal injury.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fmicb.2025.1649947","type":"journal-article","created":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:33:20Z","timestamp":1762929200000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Regulatory effects of berberine on intestinal microecology in mice with ulcerative colitis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xinyi","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingyu","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Tang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zonglang","family":"Lai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,11,12]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"147","DOI":"10.2147\/CEG.S375969","article-title":"Emerging therapies for ulcerative colitis: updates from recent clinical trials","volume":"16","author":"AlAmeel","year":"2023","journal-title":"Clin. Exp. Gastroenterol."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1053\/j.gastro.2015.03.001","article-title":"Clinical practice guidelines for the medical management of nonhospitalized ulcerative colitis: the Toronto consensus","volume":"148","author":"Bressler","year":"2015","journal-title":"Gastroenterology"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"17","DOI":"10.2174\/13816128130105","article-title":"Novel pharmacologic approaches to the prevention and treatment of ulcerative colitis","volume":"19","author":"Deng","year":"2013","journal-title":"Curr. Pharm. Des."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1496023","DOI":"10.3389\/fmed.2025.1496023","article-title":"Studies on the alleviating effect of Bifidobacterium lactis V9 on dextran sodium sulfate-induced colitis in mice","volume":"12","author":"Duan","year":"2025","journal-title":"Front. Med."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1093\/ije\/dyx275","article-title":"An introduction to instrumental variables for epidemiologists","volume":"47","author":"Greenland","year":"2018","journal-title":"Int. J. Epidemiol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"26816","DOI":"10.1038\/s41598-024-78603-z","article-title":"Causal association of gut microbes and blood metabolites with acne identified through systematic mendelian randomization","volume":"14","author":"He","year":"2024","journal-title":"Sci. Rep."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"17948","DOI":"10.1038\/srep17948","article-title":"PDGFR\u03b1 plays a crucial role in connective tissue remodeling","volume":"5","author":"Horikawa","year":"2015","journal-title":"Sci. Rep."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"937029","DOI":"10.3389\/fphar.2022.937029","article-title":"Pharmacological effects of berberine on models of ulcerative colitis: a meta-analysis and systematic review of animal studies","volume":"13","author":"Hu","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref9","first-page":"1","article-title":"Palmatine regulates bitter signal and suppresses inflammatory response to improve DSS-induced ulcerative colitis","author":"Huang","year":"2025","journal-title":"Chin. J. Immunol."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3390\/ph18020193","article-title":"Perspectives on Berberine and the regulation of gut microbiota: as an anti-inflammatory agent","volume":"18","author":"Jael Teresa de Jes\u00fas","year":"2025","journal-title":"Pharmaceuticals (Basel)"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/s41572-020-0205-x","article-title":"Ulcerative colitis","volume":"6","author":"Kobayashi","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"105972","DOI":"10.1016\/j.phrs.2021.105972","article-title":"Natural-derived alkaloids exhibit great potential in the treatment of ulcerative colitis","volume":"175","author":"Li","year":"2022","journal-title":"Pharmacol. Res."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e0160724","DOI":"10.1128\/msystems.01607-24","article-title":"Gut commensal Alistipes shahii improves experimental colitis in mice with reduced intestinal epithelial damage and cytokine secretion","volume":"10","author":"Lin","year":"2025","journal-title":"mSystems"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"7696","DOI":"10.1073\/pnas.84.21.7696","article-title":"Role of platelet-derived growth factor in wound healing: synergistic effects with other growth factors","volume":"84","author":"Lynch","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"1528","DOI":"10.1002\/ibd.20512","article-title":"Contributions of IBD5, IL23R, ATG16L1, and NOD2 to Crohn\u2019s disease risk in a population-based case-control study: evidence of gene-gene interactions","volume":"14","author":"Okazaki","year":"2008","journal-title":"Inflamm. Bowel Dis."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"906","DOI":"10.3389\/fimmu.2020.00906","article-title":"The genus Alistipes: gut Bacteria with emerging implications to inflammation, Cancer, and mental health","volume":"11","author":"Parker","year":"2020","journal-title":"Front. Immunol."},{"key":"ref17","volume-title":"Effect of compound phytonutrients on rumen health, Bacteria and metabolites in mutton sheep","author":"Su","year":"2024"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1124\/mol.116.106617","article-title":"Orally administered Berberine modulates hepatic lipid metabolism by altering microbial bile acid metabolism and the intestinal FXR signaling pathway","volume":"91","author":"Sun","year":"2017","journal-title":"Mol. Pharmacol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"2407","DOI":"10.3390\/nu15102407","article-title":"The effects of specific gut microbiota and metabolites on IgA nephropathy-based on Mendelian randomization and clinical validation","volume":"15","author":"Wang","year":"2023","journal-title":"Nutrients"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1370919","DOI":"10.3389\/fmolb.2024.1370919","article-title":"Causal associations among gut microbiota, 1400 plasma metabolites, and asthma: a two-sample Mendelian randomization study","volume":"11","author":"Wang","year":"2024","journal-title":"Front. Mol. Biosci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1038\/s41522-023-00420-5","article-title":"Bacteroides uniformis-induced perturbations in colonic microbiota and bile acid levels inhibit TH17 differentiation and ameliorate colitis developments","volume":"9","author":"Yan","year":"2023","journal-title":"NPJ Biofilms Microbiomes"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1187718","DOI":"10.3389\/fnut.2023.1187718","article-title":"Berberine influences multiple diseases by modifying gut microbiota","volume":"10","author":"Yang","year":"2023","journal-title":"Front. Nutr."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"511","DOI":"10.13381\/j.cnki.cjm.202205003","article-title":"Comparison of microflora from intestinal mucosavscecal contents in mice with ulcerative colitis","volume":"34","author":"Yin","year":"2022","journal-title":"Chin. J. Microecol."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1987779","DOI":"10.1080\/19490976.2021.1987779","article-title":"Depression and anxiety in patients with active ulcerative colitis: crosstalk of gut microbiota, metabolomics and proteomics","volume":"13","author":"Yuan","year":"2021","journal-title":"Gut Microbes"},{"key":"ref25","doi-asserted-by":"publisher","first-page":"849","DOI":"10.13381\/j.cnki.cjm.202107022","article-title":"Interaction between gut microbiota and bile acid metabolism","volume":"33","author":"Zeng","year":"2021","journal-title":"Chin. J. Microecol."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"3374","DOI":"10.3892\/etm.2017.4402","article-title":"Berberine alleviates dextran sodium sulfate-induced colitis by improving intestinal barrier function and reducing inflammation and oxidative stress","volume":"13","author":"Zhang","year":"2017","journal-title":"Exp. Ther. Med."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1502849","DOI":"10.3389\/fmed.2024.1502849","article-title":"T helper cell 17\/regulatory T cell balance regulates ulcerative colitis and the therapeutic role of natural plant components: a review","volume":"11","author":"Zhao","year":"2024","journal-title":"Front. Med."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"101885","DOI":"10.1016\/j.gassur.2024.101885","article-title":"Effects of gut microbiota and metabolites on pancreatitis: a 2-sample Mendelian randomization study","volume":"29","author":"Zhao","year":"2025","journal-title":"J. Gastrointest. Surg."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1016\/j.intimp.2018.12.036","article-title":"Protective effects of berberine hydrochloride on DSS-induced ulcerative colitis in rats","volume":"68","author":"Zhu","year":"2019","journal-title":"Int. Immunopharmacol."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1083788","DOI":"10.3389\/fimmu.2022.1083788","article-title":"Berberine a traditional Chinese drug repurposing: its actions in inflammation-associated ulcerative colitis and cancer therapy","volume":"13","author":"Zhu","year":"2022","journal-title":"Front. Immunol."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"e0001421","DOI":"10.1128\/IAI.00014-21","article-title":"Cross talk between gut microbiota and intestinal mucosal immunity in the development of ulcerative colitis","volume":"89","author":"Zou","year":"2021","journal-title":"Infect. Immun."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"101462","DOI":"10.1016\/j.bbrep.2023.101462","article-title":"Platelet-derived growth factor PDGF-AA upregulates connexin 43 expression and promotes gap junction formations in osteoblast cells through p-Akt signaling","volume":"34","author":"Zuo","year":"2023","journal-title":"Biochem. Biophys. Rep."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1649947\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T06:33:24Z","timestamp":1762929204000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2025.1649947\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,12]]},"references-count":32,"alternative-id":["10.3389\/fmicb.2025.1649947"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2025.1649947","relation":{},"ISSN":["1664-302X"],"issn-type":[{"value":"1664-302X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,12]]},"article-number":"1649947"}}